DESCRIPTION: The goal of this research is to furnish an understanding of the complex neural substrates underlying the regulation of the circadian oscillator located in the hypothalamic suprachiasmatic nucleus (SCN), which functions as our biological clock. Photic information essential for daily phase resetting of the SCN circadian clock is conveyed directly to the SCN from retinal ganglion cells via the retinohypothalamic tract (RHT). The SCN also receives a dense serotonergic innervation arising from the midbrain raphe. RHT and serotonergic afferents are coextensive in the SCN and serotonergic agonists can modify the pacemakers response to light. In this proposal the applicants will test the hypothesis that the 5HT1B receptor subtype is located presynaptically on retinal axon terminals in the SCN and that it plays a major role in regulating photic input to the SCN. Using behavioral analysis of wheel running activity the applicants will test whether 5HT1B receptors mediate serotonergic inhibition of light-induced phase shifts in hamsters and in transgenic knockout mice lacking the 5HT1B receptor. Using morphological techniques the applicants will test whether the 5HT1B receptor can regulate the light-induce expression of c-Fos protein in SCN neurons, and more critically examine the expression of 5HT1B receptors in RHT terminals. Finally, using patch clamp electrophysiology the applicants will test the effects of 5HT on RHT-SCN synaptic transmission in slices from both hamsters and knockout mice.